It has been widely known for many years that the mucus layer lining an epithelium represents an important transport barrier for a variety of nutrients and xenobiotics. None of the existing cellular or mathematical models are appropriate in studying the subject. In this pilot study, we propose to develop a nonmammalian model utilizing the HT29-18N2 cell monolayer. The HT29-18N2 cell line is a subclone of the human colon adenocarcinoma cell line HT29. When grown on a permeable membrane in a medium in which glucose is replaced with galactose, the cells differentiate to mucin-secreting goblet-like cells. The cell monolayer should provide an ideal system for quantitative studies on the effects of the mucus layer on the overall transepithelial transport of various solutes. The present study addresses three specific questions using simple probe molecules which undergo the transport via non-specific passive diffusional processes: How does the mucus layer affect (1) the well-known sigmoidal profile of the permeability-lipophilicity relationship? (2) the transport of different ionic species at a given lipophilicity? and (3) the paracellular transport of neutral polar substances of different MW? Once validated, the system should enjoy a wide range of applications ranging from the nasal to G.I. absorption of therapeutic agents.